This proposal is designed to further develop three types of vaccine candidates: recombinant stress protein fusions, HIV and SIV genome-less particles, and live recombinant BCG vehicles that express antigens and lymphokines. We plan to engineer novel recombinant fusion proteins that incorporate mycobacterial stress proteins and retroviral proteins, exploiting the unusual immunological properties of stress proteins. We will continue to develop genetically inactivated HIV/SIV particles as vaccine candidates by constructing stable cell lines that produce the noninfectious retroviral mutants particles. We will also continue to generate and test the immune response to new forms of recombinant BCG vaccines, especially those that secrete interleukin. We are undertaking the simultaneous development of these three vaccine candidates because we recognize that an efficacious HIV vaccine may require multiple components. Our strategy is to investigate the humoral and cellular immune response to each reagent in mice, to optimize conditions required for eliciting CD8+ CTL, and to provide these data and reagents to investigators in other NCVDG programs and at NIAID for further studies in primates. The stress protein fusions, genetically inactivated retroviral particles, and BCG recombinants will be provided to specific NCVDGs and to NIAID for tests of efficacy in animal models. A vaccine study with BCG-SIV recombinants is already underway in collaboration with the NCVDG under Dr. Murray Gardner. The long-term goals of this research program are to improve our understanding of HIV biology and immunology and to develop an HIV vaccine candidate.
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